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A well-tolerated regimen of 800 cGy TBI-fludarabine-busulfan-ATG for reliable engraftment after unmanipulated haploidentical peripheral blood stem cell transplantation in adult patients with acute myeloid leukemia.
Biol Blood Marrow Transplant. 2015 Jan; 21(1):119-29.BB

Abstract

Eighty adult patients with acute myeloid leukemia (AML) received peripheral blood T cell-replete HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Disease status at transplantation was either first or second complete remission (CR, n = 69) or relapse/refractory (n = 11). Identical transplant-related procedures with conditioning regimen consisting of fractionated 800 cGy total body irradiation (TBI), fludarabine (30 mg/m(2)/day for 5 days), busulfan (3.2 mg/kg/day for 2 days), and antithymocyte globulin (1.25 mg/kg/day on days -4 to -1) and graft-versus-host disease (GVHD) prophylaxis with tacrolimus and methotrexate were used in all patients. Recovery of neutrophil (median, 11 days) and platelet (median, 10 days) counts was achieved in all patients with full donor chimerism (≥ 99%), and no delayed engraftment failure was observed. The cumulative incidence of grades III to IV acute GVHD and moderate to severe chronic GVHD was 11.2% and 26.3%, respectively. A donor CD8(+) and CD4(+) T cell dose above the median value was significantly associated with the incidences of grades II to IV acute GHVD and moderate to severe chronic GVHD, respectively. After a median follow-up of 28 months for survivors, the 2-year cumulative incidences of relapse (n = 20) and nonrelapse mortality (n = 10) were 26.6% and 12.2%, respectively. Although all but 1 patient in relapse/refractory status died, the 2-year overall and progression-free survival of patients in first CR was 82.5% and 75.1%, respectively. We suggest the strategy of fractionated 800 cGy TBI-based conditioning with unmanipulated peripheral blood stem cell grafts seems feasible with favorable outcomes for adult patients with AML undergoing haplo-HSCT in CR.

Authors+Show Affiliations

Department of Hematology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Cancer Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Cancer Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Cancer Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Cancer Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: cumckim@catholic.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25300871

Citation

Yahng, Seung-Ah, et al. "A Well-tolerated Regimen of 800 cGy TBI-fludarabine-busulfan-ATG for Reliable Engraftment After Unmanipulated Haploidentical Peripheral Blood Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 21, no. 1, 2015, pp. 119-29.
Yahng SA, Kim JH, Jeon YW, et al. A well-tolerated regimen of 800 cGy TBI-fludarabine-busulfan-ATG for reliable engraftment after unmanipulated haploidentical peripheral blood stem cell transplantation in adult patients with acute myeloid leukemia. Biol Blood Marrow Transplant. 2015;21(1):119-29.
Yahng, S. A., Kim, J. H., Jeon, Y. W., Yoon, J. H., Shin, S. H., Lee, S. E., Cho, B. S., Eom, K. S., Kim, Y. J., Lee, S., Min, C. K., Cho, S. G., Kim, D. W., Lee, J. W., Min, W. S., Park, C. W., & Kim, H. J. (2015). A well-tolerated regimen of 800 cGy TBI-fludarabine-busulfan-ATG for reliable engraftment after unmanipulated haploidentical peripheral blood stem cell transplantation in adult patients with acute myeloid leukemia. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 21(1), 119-29. https://doi.org/10.1016/j.bbmt.2014.09.029
Yahng SA, et al. A Well-tolerated Regimen of 800 cGy TBI-fludarabine-busulfan-ATG for Reliable Engraftment After Unmanipulated Haploidentical Peripheral Blood Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia. Biol Blood Marrow Transplant. 2015;21(1):119-29. PubMed PMID: 25300871.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A well-tolerated regimen of 800 cGy TBI-fludarabine-busulfan-ATG for reliable engraftment after unmanipulated haploidentical peripheral blood stem cell transplantation in adult patients with acute myeloid leukemia. AU - Yahng,Seung-Ah, AU - Kim,Jung-Ho, AU - Jeon,Young-Woo, AU - Yoon,Jae-Ho, AU - Shin,Seung-Hwan, AU - Lee,Sung-Eun, AU - Cho,Byung-Sik, AU - Eom,Ki-Seong, AU - Kim,Yoo-Jin, AU - Lee,Seok, AU - Min,Chang-Ki, AU - Cho,Seok-Goo, AU - Kim,Dong-Wook, AU - Lee,Jong-Wook, AU - Min,Woo-Sung, AU - Park,Chong-Won, AU - Kim,Hee-Je, Y1 - 2014/10/06/ PY - 2014/04/30/received PY - 2014/09/30/accepted PY - 2014/10/11/entrez PY - 2014/10/11/pubmed PY - 2015/8/14/medline KW - Acute myeloid leukemia KW - Haploidentical hematopoietic stem cell transplantation KW - T cell replete KW - Total body irradiation SP - 119 EP - 29 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 21 IS - 1 N2 - Eighty adult patients with acute myeloid leukemia (AML) received peripheral blood T cell-replete HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Disease status at transplantation was either first or second complete remission (CR, n = 69) or relapse/refractory (n = 11). Identical transplant-related procedures with conditioning regimen consisting of fractionated 800 cGy total body irradiation (TBI), fludarabine (30 mg/m(2)/day for 5 days), busulfan (3.2 mg/kg/day for 2 days), and antithymocyte globulin (1.25 mg/kg/day on days -4 to -1) and graft-versus-host disease (GVHD) prophylaxis with tacrolimus and methotrexate were used in all patients. Recovery of neutrophil (median, 11 days) and platelet (median, 10 days) counts was achieved in all patients with full donor chimerism (≥ 99%), and no delayed engraftment failure was observed. The cumulative incidence of grades III to IV acute GVHD and moderate to severe chronic GVHD was 11.2% and 26.3%, respectively. A donor CD8(+) and CD4(+) T cell dose above the median value was significantly associated with the incidences of grades II to IV acute GHVD and moderate to severe chronic GVHD, respectively. After a median follow-up of 28 months for survivors, the 2-year cumulative incidences of relapse (n = 20) and nonrelapse mortality (n = 10) were 26.6% and 12.2%, respectively. Although all but 1 patient in relapse/refractory status died, the 2-year overall and progression-free survival of patients in first CR was 82.5% and 75.1%, respectively. We suggest the strategy of fractionated 800 cGy TBI-based conditioning with unmanipulated peripheral blood stem cell grafts seems feasible with favorable outcomes for adult patients with AML undergoing haplo-HSCT in CR. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/25300871/A_well_tolerated_regimen_of_800_cGy_TBI_fludarabine_busulfan_ATG_for_reliable_engraftment_after_unmanipulated_haploidentical_peripheral_blood_stem_cell_transplantation_in_adult_patients_with_acute_myeloid_leukemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(14)00610-7 DB - PRIME DP - Unbound Medicine ER -